BACKGROUND: Atrial fibrillation (AF) has a tendency to become persistent over time and is known to induce atrial electrical, mechanical and ionic remodeling. However, the underlying mechanisms by which AF persists were not fully determined. The present study was carried out to assess alterations in the gene expression, including the oxidative stress-related genes of atrial myocardial cells in patients with persistent AF, and ultrastructural remodeling, as assessed by electron microscopy (EM) in pacing-induced sustained AF canine models. METHODS: cDNA microarray technique and Western blot studies were performed, with tissue samples (right atrial appendage) from 10 patients, 4 with persistent AF and 6 used as controls, which had undergone coronary artery bypass surgery. Four dogs were subjected to continuous left atrial pacing at 400 bpm for at least 12 weeks to induce AF. One dog in sinus rhythm was used as a control sham operation. Tissue samples (1 mm3) were obtained from 4 sites of both atria for EM examination. RESULTS: Thirty up-regulated and 25 down-regulated gene expressions were observed in the patients with AF. Eight of the up-regulated and 6 of the down-regulated genes were oxidative stress-related, which were confirmed by Western blot analyses. The characteristics of ultrastructural remodeling by persistent AF were: 1) an increased number of minimitochondria, 2) disarrayed myofilaments, 3) rarefaction of myofilaments, 4) disintegrated cristae and alignment in mitochondria and 5) vacuolization. CONCLUSIONS: Persistent AF leads to alterations in the gene expression related to oxidative stress in the atrium, and also results in ultrastructural changes similar to those of an ischemia-reperfusion injury.
Animals ; Atrial Fibrillation* ; Blotting, Western ; Coronary Artery Bypass ; Dogs ; Gene Expression* ; Humans ; Microscopy, Electron ; Mitochondria ; Muscle Cells ; Myofibrils ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress ; Reperfusion Injury

Chronic hemodialysis patients frequently experience hemodialysis(HD)-related side effects caused by excessive ultrafiltration and abrupt change of osmolality. Sodium ramping in HD is known to reduce ultrafiltration-related side effects, but it frequently induces symptoms related to sodium overload. We wanted to know the relationship between blood volume changes and the side effects related to ultrafiltration during hemodialysis and whether we can individualize various sodium ramping methods according to the effect of change in blood volume( BV) and side effects of sodium ramping. We studied 9 hypotension-prone patients during HD. The duration of the study lasted for 5 weeks, each week using different sodium ramping protocols: protocol 1; dialysate [Na+] of 140mEq/L, protocol 2; dialysate [Na+] same as the predialysis serum [Na+], protocol 3; dialysate [Na+] was 20mEq/L greater than that of the patient's serum for 1hr, 10mEq/L greater than patient's serum [Na+] for 2hr and then the same as patient's serum [Na+] for the last 1hr, protocol 4; at the beginning of dialysis, dialysate sodium was ramped to 20mEq/L above the patient's serum sodium and then on a straight linear fashion lowered to the predialysis serum [Na+] at the end of dialysis, protocol 5; sodium was constantly ramped to 10 mEq/L above serum [Na+]. We measured the BV with Crit-Line IIR(In-Line Diagnostics, Corp., Riverdale, USA), the blood pressure during each HD and interdialytic weight gain. We documented subjective symptoms which occurred during the 5 treatment protocols by patient's questionnaire after each HD. The results were as follows. 1) The mean age of the patients(M:F=3:6) was 54.1years and 6 patients were diabetics. 2) There was no significant difference in the BV among the 5 protocols in both whole study population and individual. Neither was there a statistically significant difference in the BV with respect to hypotension during HD. 3) There were no episodes of hypotension(P value <0.001) with protocols 3, 4, 5 compared to protocols 1 and 2. 4) Three patients during protocols 4 and 5 experienced more thirst after HD than during protocol 1 and one patient during protocol 4, 5 had more interdialytic weight gain than the protocol 1. As a whole, patients while on protocol 4 & 5 experienced more thirst than protocol 1 but patients during protocol 3 experienced the same degree of thirst as protocol 1. In summary, sodium ramping reduced HD-related side effects but this benefit could not be explained on the basis of blood volume change measured by the Crit-Line IIR. Protocol 3 may be more appropiate sodium ramping method in 4 of the 9 patients. These data suggest that protocol 3 may be used before protocol 4, 5 when we apply sodium ramping to the patients who frequently have hypotension during HD.
Architectural Accessibility* ; Blood Pressure ; Blood Volume* ; Clinical Protocols ; Dialysis ; Humans ; Hypotension ; Osmolar Concentration ; Renal Dialysis* ; Sodium* ; Thirst ; Ultrafiltration ; Weight Gain ; Surveys and Questionnaires